Recent developments in the understanding of the failure of cardiovascular implants has led both the scientific and industrial communities searching for alternatives to provide optimum products. Over the past ten years, rapid advances in cell and molecular biology methodologies have led to a significant expansion of our knowledge base in vascular biology which potentially has application in every area of cardiovascular surgery and implant design. In recognition of the critical role that cell physiology, molecular biology, and other biomedical sciences play in improving implant performance, research and development efforts in cardiovascular implant science and engineering have recently focused on developing engineered biohybrid biomaterials that utilize synthetic biomaterials as well as cells, biochemicals, and extracellular matrix of cardiovascular tissues to develop a new generation of cardiovascular implants and related products that have more specific and longer-term performance goals than products that are currently on the market. The proposed work focuses on developing and applying biohybrid technologies for synthetic vascular grafts. Overall goal of the proposed study: Develop and evaluate the following four biohybrid technologies for improved performance of synthetic vascular grafts using specific implants and animal models currently under investigation by the PI: 1) bioactive biomaterial surface modifications; 2) bioactive degradable hydrogels; and 3) local drug/gene delivery systems and therapies. Hypotheses: The above described b1ohybrid technologies, namely bioactive biomaterial surface modifications, bioactive degradable hydrogels, and local drug/gene delivery system s/therapies will promote significant gains in long-term performance of synthetic vascular grafts. Combinations of these applied technologies will work in synergy to maximize graft performance. Aims: 1) Develop bioactive surface modifications on ePTFE (expanded polytetrafluoroethylene) vascular grafts and assess their effects on implant performance in vivo; 2) Develop degradable hydrogel formulations that can be impregnated into the porous space of ePTFE grafts for promoting angiogenesis in host tissues surrounding the implant, neovascularization of the ePTFE graft wall and luminal endothelialization via transmural growth of neovascular tissue; 3) Develop degradable hydrogel delivery vehicles that can be impregnated into ePTFE grafts for local drug/gene therapies targeting graft hyperplasia; and 4) Compare the impact of combinations of biohybrid technologies on graft performance to single technology approaches. Overall the proposed work will define biohybrid technologies that have promise for clinical application and will set the stage for further technology development. (End of Abstract)